The Lexington VA Medical Center requests funds to acquire a Thermo Scientific Q-Exactive Plus hybrid mass spectrometer with a nano-electrospray ionization source and an UltiMate 3000 RSLC nano HPLC as an integrated nano-LC-MS/MS system. The goal of this application is to provide advanced mass spectrometry capabilities to meet the proteomics needs of 7 highly productive VA- funded investigators at the Lexington VA Medical Center. The Q Exactive hybrid mass spectrometer offers a combination of a quadrupole and an advanced and high precision electrostatic ion trap (Orbitrap) mass analyzers. In comparison to the existing mass spectrometers for protein and peptide analysis, this hybrid instrument simultaneously provides high sensitivity (attomoles), high spectrum repetition rates, high mass resolution (140,000 HWFM) and high mass accuracy (< 3ppm with eternal calibration and < 1ppm with internal calibration). Moreover, it provides a versatile system capable of carrying out both qualitative and quantitative proteomic workflows. This equipment is essential to these ongoing research programs and to stimulating and enabling new collaborative research initiatives on protein identification, posttranslational modification characterization, and functional proteomics. Currently, there is no proteomic instrument at the Lexington VA Medical Center. The purchase of the instrument is critical to the continuing expansion and enhancement of the proteomics research program in human disease at VA. As described in this application, 7 VA-funded (major users) and 3 NIH/NSF-funded (minor users) investigators have specific needs for this mass spectrometer. The research projects to be supported by this instrument address critically important health challenges faced by Veterans, spanning major disease areas such as neurological disorders, cardiovascular diseases, metabolic syndrome, respiratory disease, chronic pain and alcohol abuse. The PI has over 15 years experience in the area of biological mass spectrometry and proteomics. An Advisory Committee with both VA and University investigators is assembled for overall guidance for the usage of the shared instrument. The requested instrument will have a major and long term impact on research capabilities at the Lexington VA Medical Center.